Efavirenz, a commonly used HIV medication, may cause worsening vascular function and bone problems. The purpose of this study is to determine if switching efavirenz to raltegravir, a newer HIV medication, will improve vascular function and tests of bone health.

A Randomized Controlled Pilot Trial Comparing Continued Antiretroviral Therapy With Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) With Switch to Tenofovir/Emtricitabine/Raltegravir (TDF/FTC/RAL) on Changes in Endothelial Function and Markers of Bone Metabolism

Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

Other Name: Truvada

Drug: Raltegravir

Efavirenz will be switched to raltegravir 400mg orally twice daily while continuing tenofovir/emtricitabine

Other Name: Isentress

Detailed Description:

Cardiovascular disease (CVD) is an increasingly important comorbidity in HIV-infected patients. Our preliminary data suggests that efavirenz may worsen endothelial function, which in turn may increase the risk for future CVD events. Efavirenz has also been linked to lower vitamin D levels, which may in turn result in increased bone fragility. Raltegravir is not known to affect either endothelial function or vitamin D levels. Therefore, switching efavirenz to raltegravir in patients with suppressed HIV viremia may lead to improved outcomes.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection, documented by (1) any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or (2) by two detectable HIV-1 antigens, or (3) two detectable plasma HIV-1 RNA viral loads.

Age equal to or greater than 18 years.

Receipt of TDF/FTC/EFV as the subject's initial ART regimen for at least one year prior to Screening.

Note: Interruptions in TDF/FTC/EFV of up to 10 days total during the 90 days prior to screening are allowed.

Note: Subjects who had received 3TC (lamivudine) with TDF/EFV as part of their initial regimen but have received TDF/FTC/EFV for at least one year prior to screening will be eligible.

HIV-1 RNA level <50copies/mL at screening and with a history of having an HIV-1 RNA level of <50copies/mL between 1 and 6 months prior to screening.

At least one genotypic resistance test done prior to initiation of TDF/FTC/EFV suggesting no evidence of antiretroviral resistance to any nucleos(t)ide reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor.

No previous use of raltegravir or other integrase inhibitor.

For women of reproductive potential, a negative urine pregnancy test at screening and willingness to use two forms of birth control during the course of the study. Acceptable forms of birth control include condoms (with or without a gel that can kill sperm), a diaphragm or cervical cap (with or without a gel that can kill sperm), an intrauterine device (IUD), or hormonal-based birth control ("the pill").

Note: Fever within 48 hours prior to each main study visit will require postponement of that study visit until the patient has defervesced (T < 38.0C) for at least 48 hours; fevers continuing past the allowed study visit timeframe will result in study discontinuation.

Therapy for acute infection or other serious medical illnesses within 14 days prior to screening.

Note: Therapy for acute infection or other serious medical illnesses that overlaps with a main study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.

Pregnancy or breastfeeding during the course of the study.

Hypotension, defined as systolic blood pressure < 90mmHg, at time of screening.

Note: Hypotension noted prior to brachial artery reactivity testing on each main study visit will result in study visit postponement of at least one day until systolic pressure is ≥ 90mmHg the morning of brachial reactivity testing; postponement outside of the allowed study visit timeframe will result in study discontinuation.

Receipt of lipid-lowering drugs or anticonvulsants (defined as those drugs with significant CYP 450 induction or inhibition) screening.

Use of sildenafil, vardenafil, or tadalafil within 72 hours (before or after) of each main study visit.

Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01270802